Exercise-training is used widely in the rehabilitation of patients with coronary artery disease (CAD). However, it is not clear whether myocardial blood supply (as opposed to a peripherally mediated decrease in the work load and O2 requirement of the heart) can be improved by exercise-training in patients with CAD. The objective of our research is to determine whether 12 months of exercise-training of progressively increasing duration, intensity and frequency can improve blood supply to underperfused regions of myocardium in patients with CAD. The most important of the methodological approaches we are using to achieve this goal are: a) Radionuclide ventriculography with technetium-99m. To evaluate the effect of training on myocardial blood supply, we use radionuclide ventriculography to determine the responses of, initially abnormal, global and regional ejection fractions to dynamic and isometric exercise tests. Exercise in the tests performed after 12 mo of training is adjusted to result in the same, or higher, heart rate x systolic blood pressure as was attained prior to training. We interpret a significant improvement in the response of global and regional ejection fractions to exercise that elicits the same heart rate x systolic blood pressure as evidence for an improvement in myocardial blood supply. b) Exercise electrocardiography. In our electrocardiographic evaluation of the effect of exercise-training on myocardial oxygenation, we are determining the HR x systolic BP threshold for ST depression. c) Myocardial perfusion imaging with thallium-201. Our approach is to obtain exercise and resting 201T1 scans before and after 12 mo of exercise-training. We interpret the absence, or clear cut reduction in size, after training, of an exercise-induced perfusion defect that was present before training as evidence of an improved myocardial blood supply (but only if there are concomitant improvements in work capacity, VO2max and exercise electrocardiogram). d) Echocardiographic assessment of left ventricular function by measurement of the responses of mean velocity of circumferential fiber shortening and extent of fiber shortening to isometric exercise.